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Article

Zebrafish Model as a Screen to Prevent Cyst Inflation in Autosomal Dominant Polycystic Kidney Disease

1
CEDOC, Chronic Diseases Research Center, NOVA Medical School|Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo Mártires da Pátria, 130, 1169-056 Lisboa, Portugal
2
Department of Nephrology, Centro Hospitalar e Universitário de Lisboa Central, Hospital de Curry Cabral, Rua da Beneficência, 8, 1069-166 Lisboa, Portugal
3
ToxOmics, Center of ToxicoGenomics & Human Health, NOVA Medical School|Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo Mártires da Pátria, 130, 1169-056 Lisboa, Portugal
*
Authors to whom correspondence should be addressed.
Academic Editors: Andrea Huwiler and Giuseppe Novelli
Int. J. Mol. Sci. 2021, 22(16), 9013; https://doi.org/10.3390/ijms22169013
Received: 20 June 2021 / Revised: 5 August 2021 / Accepted: 17 August 2021 / Published: 20 August 2021
(This article belongs to the Special Issue Molecular Mechanisms and Therapies for Kidney Diseases)
In autosomal dominant polycystic kidney disease (ADPKD), kidney cyst growth requires the recruitment of CFTR (cystic fibrosis transmembrane conductance regulator), the chloride channel that is defective in cystic fibrosis. We have been studying cyst inflation using the zebrafish Kupffer’s vesicle (KV) as model system because we previously demonstrated that knocking down polycystin 2 (PC2) induced a CFTR-mediated enlargement of the organ. We have now quantified the PC2 knockdown by showing that it causes a 73% reduction in the number of KV cilia expressing PC2. According to the literature, this is an essential event in kidney cystogenesis in ADPKD mice. Additionally, we demonstrated that the PC2 knockdown leads to a significant accumulation of CFTR-GFP at the apical region of the KV cells. Furthermore, we determined that KV enlargement is rescued by the injection of Xenopus pkd2 mRNA and by 100 µM tolvaptan treatment, the unique and approved pharmacologic approach for ADPKD management. We expected vasopressin V2 receptor antagonist to lower the cAMP levels of KV-lining cells and, thus, to inactivate CFTR. These findings further support the use of the KV as an in vivo model for screening compounds that may prevent cyst enlargement in this ciliopathy, through CFTR inhibition. View Full-Text
Keywords: autosomal dominant polycystic kidney disease (ADPKD); cystic fibrosis transmembrane conductance regulator (CFTR); Kupffer’s vesicle (KV); polycystin-2 (PC2) autosomal dominant polycystic kidney disease (ADPKD); cystic fibrosis transmembrane conductance regulator (CFTR); Kupffer’s vesicle (KV); polycystin-2 (PC2)
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MDPI and ACS Style

Oliveira, I.; Jacinto, R.; Pestana, S.; Nolasco, F.; Calado, J.; Lopes, S.S.; Roxo-Rosa, M. Zebrafish Model as a Screen to Prevent Cyst Inflation in Autosomal Dominant Polycystic Kidney Disease. Int. J. Mol. Sci. 2021, 22, 9013. https://doi.org/10.3390/ijms22169013

AMA Style

Oliveira I, Jacinto R, Pestana S, Nolasco F, Calado J, Lopes SS, Roxo-Rosa M. Zebrafish Model as a Screen to Prevent Cyst Inflation in Autosomal Dominant Polycystic Kidney Disease. International Journal of Molecular Sciences. 2021; 22(16):9013. https://doi.org/10.3390/ijms22169013

Chicago/Turabian Style

Oliveira, Inês, Raquel Jacinto, Sara Pestana, Fernando Nolasco, Joaquim Calado, Susana S. Lopes, and Mónica Roxo-Rosa. 2021. "Zebrafish Model as a Screen to Prevent Cyst Inflation in Autosomal Dominant Polycystic Kidney Disease" International Journal of Molecular Sciences 22, no. 16: 9013. https://doi.org/10.3390/ijms22169013

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